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Biomedical subjects

L Gorman

Publications and source records attributed to L Gorman.

9 recordsLinked to original sources
PubMed1991

Basal forebrain cholinergic system: a functional analysis.

This chapter has been organized empirically, focusing on the types of approaches that have been taken to understand BFCS function. This approach reflects the state of our knowledge about the behavioral and psychological functions of the BFCS. Considerable information has been gathered in the very short time that the BFCS has been the object of intense investigation. The results from the neurotoxic lesions and from the HACU studies provide some points of consistency and some puzzling differences. Both approaches to the study of basal forebrain function suggest that the MSA is involved in tasks that require spatial working memory; MSA lesions impaired choice accuracy, and HACU in the HIP was increased after performance. The pattern of results in simpler tasks is more difficult to interpret. In a left-right reference memory discrimination in a T-maze, MSA lesions did not impair acquisition or performance, whereas HACU in the HIP was activated during performance. This pattern of results suggests that although the MSA is engaged during this type of task, its activity is not necessary for normal performance. These, and other comparisons indicate the need for a systematic analysis of task demand (Olton, 1989b). Parametric manipulations of different task demands in a systematic fashion can indicate the extent to which the BFCS is involved in the function associated with each parametric manipulation. Ultimately, of course, the organization of this material should focus on particular psychological functions, rather than the techniques and procedures used to gather the information. Achieving this goal is going to require careful attention to the design of behavioral experiments so that definitive conclusions can be made about the extent to which the BFCS is involved in a given psychological function. A systematic application of task analysis can achieve this goal (Olton, 1986, 1989a, 1989b). For example, BFCS lesions in rats impair choice accuracy in spatial working memory tasks, and performance in these tasks engages the HACU system, at least in the HIP. If the spatial functions of this task involve the BFCS, then a nonspatial version of the task should produce a different pattern of results. If the spatial nature of the task is unimportant for BFCS function, then a nonspatial version of the task should produce the same results. By systematically changing one characteristic of the task at a time, the contribution of each component can be assessed.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1990

Relationship between antecedent angina pectoris and short-term prognosis after thrombolytic therapy for acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group.

The relationship between preinfarction clinical status and short-term outcome was prospectively evaluated in 775 patients hospitalized with acute myocardial infarction after reperfusion therapy. It was anticipated that a history of angina preceding myocardial infarction by more than 7 days would be associated with more extensive underlying coronary artery disease and a more complicated in-hospital course. However, although this group did have a higher risk profile for coronary artery disease (hypertension 53.6% vs 37.2%; diabetes 22.5% vs 12.1%; hyperlipidemia 19.4% vs 9.8%; mean number of risk factors 2.2 vs 1.7, p = 0.0001), a higher incidence of multivessel disease (57.7% vs 39.6%, p less than 0.0001), worse baseline global left ventricular function (left ventricular ejection fraction 48.8% vs 51.3%, p = 0.03), and impaired function of the noninfarct zone (-0.05 vs +0.46 SD/chord, p = 0.002), the in-hospital course was less complicated than in the group without prior angina. Patients without antecedent angina had a higher rate of reocclusion of the infarct-related artery (13.6% vs 8.2%; p = 0.048). Although the difference did not reach statistical significance (7.2% vs 4.6%; p = 0.21), the in-hospital mortality rate was also higher in this group. These findings suggest that a history of prior angina is not necessarily associated with an unfavorable short-term prognosis after reperfusion therapy. This may be related to the greater prior use by this group of beta-adrenergic- and calcium channel-blocking agents (23.1% vs 8.5% and 20.7% vs 3.8%, respectively). It may also be related to the beneficial effects of collateral vessels, myocardial preconditioning, or differences in the native fibrinolytic system.

Aged↗
PubMed1989

Randomized, double-blind, placebo-controlled trial of tissue plasminogen activator in unstable angina.

Angiographic, angioscopic and pathologic reports have recently demonstrated a high incidence of intracoronary thrombus in patients with unstable angina. To determine if thrombolysis could be beneficial when combined with maximal medical therapy, 40 patients with rest angina, angiographically documented coronary artery disease and pacing-induced ischemia were randomly assigned to intravenous recombinant tissue-type plasminogen activator (rt-PA, 150 mg/8 h) or placebo in a prospective double-blind trial. All patients received nitrates, a beta-adrenergic blocking agent, a calcium channel blocker, aspirin and heparin. Pacing thresholds for ischemia and quantitative coronary stenosis were measured before and after infusion of the study medication. Intracoronary thrombus was identified angiographically before infusion of the study medication in 16 patients; 7 received rt-PA and 9 received placebo. The ischemic pacing threshold in patients treated with rt-PA increased from 112 +/- 4 beats/min at baseline to 127 +/- 5 beats/min (p = 0.007) by the end of the infusion versus an insignificant change in patients who received placebo (from 116 +/- 4 to 119 +/- 4 beats/min, p = NS). In patients with intracoronary thrombus, the ischemic pacing threshold increased 26 +/- 7 beats/min with rt-PA treatment versus 0 +/- 3 beats/min with placebo (p = 0.004). In contrast, in patients without thrombus, there was no difference in ischemic pacing threshold increments between treatment groups (7 +/- 11 beats/min for rt-PA versus 6 +/- 5 beats/min for placebo, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Coronary revascularization after intravenous tissue plasminogen activator for unstable angina pectoris: results of a randomized, double-blind, placebo-controlled trial.

To determine the role of intravenous tissue plasminogen activator (t-PA) in unstable angina, it was compared with placebo in a randomized, double-blind trial. Forty patients with angina at rest and provocable ischemia (pacing induced) had baseline coronary angiography, study drug infusion and then repeat angiography at 20 +/- 9 hours. All patients received diltiazem, nitrates, beta blockers, aspirin and intravenous heparin. During study drug infusion (150 mg over 8 hours), refractory ischemia necessitating emergency bypass surgery (CABG) or coronary angioplasty (PTCA) occurred in 4 of 20 t-PA patients compared with 1 of 20 placebo patients (p = 0.21). Before discharge, revascularization for persistent, provocable ischemia and a residual stenosis greater than or equal to 60% was as follows: t-PA patients, 8 PTCA and 7 CABG; placebo patients, 11 PTCA and 8 CABG (p = 0.39). Quantitative angiographic percent diameter stenosis of the culprit artery at baseline and follow-up was: t-PA 71 +/- 17 and 63 +/- 22; placebo 70 +/- 19 and 67 +/- 22 (difference not significant). However, 3 t-PA patients compared with no placebo patients demonstrated an insignificant (less than 60% diameter) residual stenosis and averted PTCA (p = 0.14). There were no complications of PTCA in the 8 t-PA patients; in contrast, 3 of 11 placebo patients had abrupt closure, necessitating emergency CABG in 2 (p = 0.23). Thus, intravenous t-PA in unstable angina can eliminate the need for PTCA in a few patients, does not appear to decrease the overall or emergency rate of revascularization procedures and may facilitate the safety of PTCA.

Angina Pectoris↗
PubMed1987

Community hospital administration of intravenous tissue plasminogen activator in acute myocardial infarction: improved timing, thrombolytic efficacy and ventricular function.

As an investigational fibrinolytic agent for acute myocardial infarction, intravenous recombinant tissue-type plasminogen activator (rt-PA) has been administered primarily in tertiary care and university centers. To determine the value of early initiation of such therapy, two satellite community hospital emergency rooms were established for use of rt-PA and the experience was compared among 142 consecutive patients who were transferred to a regional center for acute cardiac catheterization after intravenous rt-PA therapy. In Group I (n = 19), patients received rt-PA after interhospital transport to the regional center, but before cardiac catheterization. In Group II (n = 70), rt-PA therapy was initiated by the helicopter physician and nurse team after their arrival at the local community hospital emergency room. Group III patients (n = 53) had rt-PA administered in the local community hospital by the emergency room physician. Group III patients had earlier initiation of therapy (2.1 +/- 0.8 hours in Group III versus 3.8 +/- 1.2 hours in combined Groups I and II, p less than 0.001) and an increased rate of infarct vessel recanalization on the 90 minute coronary angiogram (81 in Group III versus 67% in combined Groups I and II, p = 0.057). The patients in Group III had a higher acute left ventricular ejection fraction (54 +/- 8% versus 50 +/- 9.5% in combined Groups I and II, p less than 0.01) and a trend toward an increased 7 day ejection fraction (55.5 +/- 9% versus 51.7 +/- 9.5%, respectively, p = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗
PubMed1986

The 1986 McCollum award lecture. Fuel-mediated teratogenesis during early organogenesis: the effects of increased concentrations of glucose, ketones, or somatomedin inhibitor during rat embryo culture.

Whole rat embryos were explanted at head-fold, late pre-somite stage (day 9.5 of gestation) and cultured in rat sera varyingly supplemented with glucose (3, 6, 9, or 12 mg/mL), D,L sodium beta-hydroxybutyrate (2, 4, 8, or 16 mM), or both (6 mg/mL D-glucose plus 8 mM beta-hydroxybutyrate). During 48 h culture, increasing glucose alone or beta-hydroxybutyrate alone effected growth retardation and faulty neural and extraneural organogenesis in dose-dependent fashion. Synergistic dysmorphogenic effects occurred when minimally teratogenic concentrations of glucose and beta-hydroxybutyrate were combined. Sera from diabetic animals containing somatomedin inhibitor bioactivity were also able to produce growth retardation and major developmental lesions in presence of amounts of glucose and ketones which of themselves were not teratogenic. Thus, aberrant fuels and fuel-related products can impair growth and organogenesis in early post-implantation embryo. Such fuel-mediated teratogenesis may be multifactorial and include possibilities for synergistic and additive interactions.

3-Hydroxybutyric Acid↗
PubMed1985

Pharmacokinetic analysis of a case of isopropanol intoxication.

A comatose 46-year-old woman, admitted to the emergency room, had isopropanol and acetone concentrations of 2000 and 120 mg/L, respectively, in her serum. She had no known history of acute isopropanol intoxication and was otherwise physically healthy. Pharmacokinetic analysis showed that the elimination of both isopropanol and its major metabolite acetone obeyed apparent first-order kinetics with half-lives of 6.4 and 22.4 h, respectively. These data contrast with the commonly held view that isopropanol is slowly metabolized. Concentrations of these analytes in cerebrospinal fluid 6 h after admission were similar to those in serum. This is the first report of the pharmacokinetics of both agents in a nonalcoholic person, and it gives the first data on concentrations of these substances in cerebrospinal fluid.

1-Propanol↗
PubMed1977

Clinical usefulness of alkaline phosphatase isoenzyme determinations.

1. We report on the clinical usefulness of alkaline phosphatase isoenzyme determinations using a combined chemical inhibition method on 731 patient serum specimens exhibiting elevated (greater than 350 U/L) alkaline phosphatase (AP) activity. 2. The relative percentages of the organ-specific alkaline phosphatase activities were computed on the basis of three independent assays: total activity, activity in the presence of 10 mMl-phenylalanine, and activity in the presence of 3.1 M urea. 3. Gamma-glutamyl transferase (GGT) activity assays were also performed on the same specimens. Using an upper reference limit of 30 U/L for GGT and comparing the GGT results with the percent liver AP, we found that the GGT results were 91% sensitive and 60% specific. 4. We conclude that AP isoenzyme determinations are very useful in identifying the organ source(s) responsible for elevated AP values. 5. The reference ranges for several age groups in relation to the adult population and their significance are presented.

Adolescent↗